Seminal reservoirs during an HIV type 1 eradication trial

Despite dramatic reduction of the levels of human immunodeficiency virus type I (HIV-1) virions in bloodand seminal plasma of infected patients, highly active antiretroviral therapy (HAART) does not eradicateHIV-1. Three patients, with less than 50 copies/ml of plasma viral RNA, were enrolled in this eradication protocol.Didanosine (DDI) and hydroxyurea (HU) were added to their baseline HAART and after a month oftherapy, low dose OKT3, followed by a 2-week course of interleukin 2 (IL-2), was administrated. All antiretroviraltherapy was then interrupted and the three patients developed viral rebound in the peripheralblood. The V3 loop region of the HIV-1 gp120 from cell-free viral RNA and proviral DNA in blood and seminalcompartments was sequenced in one patient. The two major viral isolates in semen cells were macrophage-tropic(R5) and dual-tropic (R5X4), and these isolates were also present in the PBMCs. Six months afterthe viral rebound, we demonstrated a shift toward dual tropism in semen cell-associated HIV-1 proviralDNA, with the first appearance of a T-lymphotropic (X4) provirus solely in this compartment. The virus responsiblefor the blood plasma viral rebound was never found in the semen microenvironment. This studysuggests viral compartmentalization of the semen microenvironment after an intensification and stimulatoryHIV-1 eradication protocol, with evidence of viral evolution.